1. Field of the Invention (Technical Field)
The present invention relates to small molecules, and in particular thienopyrimidine bicyclic ring core structure small molecules wherein one ring member is sulfur and two ring members are nitrogen, which bind to one or more melanocortin receptors, may be agonists, antagonists or mixed agonist-antagonists, and have utility for the treatment of melanocortin receptor-associated disorders.
2. Description of Related Art
Note that the following discussion refers to a number of publications by author(s) and year of publication, and that due to recent publication dates certain publications are not to be considered as prior art vis-a-vis the present invention. Discussion of such publications herein is given for more complete background and is not to be construed as an admission that such publications are prior art for patentability determination purposes.
A family of melanocortin receptor types and subtypes have been identified, including melanocortin-1 receptors (MC1-R) expressed on normal human melanocytes and melanoma cells, melanocortin-2 receptors (MC2-R) for ACTH (adrenocorticotropin) expressed in cells of the adrenal gland, melanocortin-3 and melanocortin-4 receptors (MC3-R and MC4-R) expressed primarily in cells in the hypothalamus, mid-brain and brainstem, and melanocortin-5 receptors (MC5-R), expressed in a wide distribution of tissues.
In general, compounds specific for MC1-R are believed to be useful for treatment of melanoma. Compounds specific for MC3-R or MC4-R are believed to be useful in regulation of energy homeostasis, including use as agents for attenuating food intake and body weight gain, for use in treatment of anorexia, as a weight gain aid, for treatment of obesity, and other treatment of other food intake and metabolism-related purposes. Compounds specific for MC3-R and MC4-R, among other melanocortin receptors, can be used as agents for treatment of sexual dysfunction, including male erectile dysfunction. Other melanocortin receptor-specific compounds, such as MCR-1 agonists, can be used as tanning agents to increase melanin production. Compounds specific for MCR-1 and MCR-3 may be useful in regulation of inflammatory processes.
There are thienopyrimidine compounds with pendant aromatic groups that are known, such as those disclosed in U.S. Pat. No. 6,340,868 and U.S. patent application Ser. No. 2004/0254198. However, these compounds are asserted to be antagonists for gonadotropin releasing hormone in the case of U.S. Pat. No. 6,340,868, and useful for autoimmune disease in the case of U.S. patent application Ser. No. 2004/0254198. There are no described thienopyrimidine compounds that are specific for one or more melanocortin receptors, or which are either agonists or antagonists with respect to one or more melanocortin receptors.
There is a significant need for compounds with high specificity for discrete melanocortin receptors, as well as compounds that are either agonists or antagonists for specific melanocortin receptors. High affinity compounds for melanocortin receptors can be used to exploit varied physiological responses associated with the melanocortin receptors, as agonists, antagonists, inverse agonists, antagonists of inverse agonists or low or functionally inactive compounds. In addition, melanocortin receptors have an effect on the activity of various cytokines, and high affinity compounds for melanocortin receptors can be used to regulate cytokine activity.